Given its central role in metabolism, the secretion of circulating proteins, and infectious disorders, a large number of genetic or acquired disorders could be corrected by liver-directed delivery of nucleic acids to instill beneficial functions or inhibit deleterious ones. However, a safe and effective delivery method for transferring nucleic acids molecules to hepatocytes remains to be perfected. To date, most in vivo nucleic acid delivery vehicles have been colloid particles with size grater than 50 nm. We believe that we have found an innovative strategy for the delivery of molecular conjugates of siRNA. This formulation relies upon several new innovations: the development-as a result of Phase I research- of membrane lytic polymers, the ability to reversibly mask the positive charges of these polymers until they reach an acidic environment such as the endosome/lysosome, the ability to target these masked membrane lytic polymers to hepatocytes in vivo, and the formation of siRNA-polymer conjugates that like polymers can be targeted to hepatocytes in vivo. [unreadable] [unreadable] [unreadable]